The major goal of the proposed studies is to develop a microencapsulated ricin toxin vaccine candidate that could be evaluated quickly in human clinical testing and stockpiled for use on the battlefield or to protect civilian populations. The vaccine will be based on microencapsulation technology that can be easily manufactured with current processes and can be developed as an orally or nasally administered vaccine with greater potential to protect against aerosolized ricin. Such technologies will be applicable to other aerosolizable toxins and microbial agents. A vaccine against ricin would be the only practical way to protect against the possibility use of ricin either on the battlefield or in a potential terrorist attack. Ricin is an agent that has been used as a biological warfare agent in the Mideast. Ricin is a potent, epithelially active toxin that could be deployed as a weapon by aerosolization, and for which there is no known effective antidote or vaccine. Lung damage caused by inhalation of ricin toxin is quick and irreversible. The ideal formulation for advancing to clinical studies would be an orally administered vaccine, eliciting secretory antibodies that neutralize toxin at the surface of the lung. The proposed research will focus on the development of formulations of a genetically inactivated ricin A chain that lacks residual toxicity but retains full immunogenicity and thus is considered to be one of the most promising and viable ricin vaccine candidates to date. We are proposing to develop ricin vaccine formulations based on microencapsulated controlled-release polymeric vehicles. The formulations will be evaluated in animals via oral, intranasal and parenteral immunization. Based on the outcomes of these studies, a candidate for clinical development will emerge. The research will center around encapsulating recombinant ricin toxin A chain mutant in controlled release polymer vehicles and evaluating the adjuvant effect in rodent models by oral, intranasal and parenteral immunization. For initial studies, the controlled release systems will be selected for evaluation based on past evidence of efficacy in animal studies with toxoided ricin (formaldehyde-inactivated holotoxin) or with other antigens, the existence of manufacturing techniques and processes that can be scaled up to commercial production levels, evidence of compatibility and stability of ingredients, and a history of safety in human vaccines or other controlled release drug products.